• Usually bilateral; unilateral polyps should prompt consideration of alternative diagnoses (inverting papillomas, nasal tumors, etc.)
• Usually arise from middle meatus and ethmoid cells (rarely from inferior turbinates)

CRScNP

Allergic Fungal Rhinosinusitis (AFRS)

CRSsNP

• ≥2 of the cardinal signs of sinusitis
  • Anosmia may be more frequent than in other types of CRS
• Objective documentation with rhinoscopy or sinus CT
• Bilateral nasal polyps in middle meatus

• ≥2 of the cardinal signs of sinusitis
• Objective documentation with rhinoscopy or sinus CT
• Positive fungal stain (hyphae) or culture of allergic mucin (obtained via surgery)
• IgE-mediated fungal allergy (via skin or in-vitro test)

• ≥1 opacified sinus on CT despite therapy (antibiotics and oral steroids); least specific finding for AFRS
• Characteristic CT hyperdensities within the opacified sinuses, which suggest accumulated allergic mucin
  • Not entirely specific for AFRS and are not required to make the diagnosis
  • Allergic mucin alone is neither highly sensitive/specific for AFRS and can be seen in other subtypes of CRS
• Evidence of IgE-mediated allergy to fungus by skin test (prick or ID) and serum specific IgE
  • Most patients show allergy to >1 fungus, although sensitization to multiple fungi is not required for the diagnosis
• Establishing the diagnosis almost always requires surgery to confirm allergic mucin which should be examined pathologically for degranulating eosinophils, fungi (by staining or culture); the pathology of sinus tissue should not show fungal invasion

• ≥2 of the cardinal signs of sinusitis
  • Facial pressure/pain may be more prominent than in in other types of CRS
• Objective documentation with rhinoscopy or sinus CT

• 20-33% of CRS
• Associated with CF (<1%, neutrophilic polyps with pediatric onset), AERD (40%), primary cililary dyskinesia (neutrophilic), Churg-Strauss
• Immunodeficiency rarely found

• 8-12% of CRS
• Advanced disease with complications of bony erosion and facial dysmorphia
• Immunodeficiency and AERD rare
• Associated fungi
  • Dematiaceous fungi most common: Bipolaris spicifera, Curvularia lunata, Exserohilum rostratum, and Alternaria spp.
  • Less common: Aspergillus fumigatus, other Aspergillus species, Epicoccum nigrum, Fusarium solani

• 60-65% of CRS
• 12% with defective/deficient antibody production
• AERD rarely found

• Sinus CT (multiplanar)
  • Consider obtaining before initial treatment of CRS because history has low predictive value
  • May demonstrate mucosal thickening, ostial obstruction, polyps, and opacification
    • Many anatomical variants (e.g., a deviated septum with a readily visualizable middle turbinate) are often misconstrued to be a polyp
    • Significant hyperplastic disease observed on a sinus CT can strongly support the diagnosis of polyps
  • Allergic mucin has characteristic ‘‘hyperdense’’ appearance and is not specific to AFRS
  • If isolated sphenoid disease or sinus wall distortion obtain MRI
• Sinus MRI
  • Further delineates allergic mucin in opacified sinus (hypoattenuated areas on T2 images)
  • Identifies multiple polyps crowded together with mucus (which have same density on CT)
• Rhinoscopy/endoscopy
  • Document purulent mucus from the middle meatus, edematous/hyperemic mucosa, polypoid changes or frank polyps. If negative exam consider imaging.
• Bacterial culture - obtain from sinus ostia only to document unusual or drug-resistant organisms
• Fungal culture of allergic mucin - due to technical difficulty may be negative despite presence of fungal hyphae on stain
• Allergy evaluation - aeroallergen sensitization found in 60% with CRS (vs. 30-40% general population)
• Immunodeficiency evaluation - immunodeficiency found in 12% with CRSsNP
  • Immunoglobulin levels, Ig subclasses, specific antibody response to pneumococcus
• Evaluation for systemic disease
  • CBC/diff, ESR
  • ANCA - found in 40-60% with Churg-Strauss, 60-90% with Wegener's
  • Serum angiotensic converting enzyme (ACE) level - elevated in 75% of untreated patients with sarcoidosis
• Total IgE and fungal IgG precipitins (for AFRS)
  • Neither total IgE levels nor fungus-specific IgG precipitins are as strikingly elevated in AFRS as in ABPA, and neither is required to establish the diagnosis
  • Total IgE often >1000 IU/mL
  • Precipitins to the implicated fungus present in most (not all) cases

• Nasal lavage >200 mL each nostril QD to multiple times daily
• Intranasal steroids
  • Nasal spray (Flonase, Nasonex, Rhinocort) up to 2 sprays each nostril BID
  • If symptoms persist: Budesonide respules 0.5 mg/2mL vial + 5 mL saline (7 mL total) each nostril followed by head-positioning QD
• LTRA - adjunct to intranasal steroids, may be more effective in patients with AERD
• Medical polypectomy - oral corticosteroids for initial treatment of nasal blockage or anosmia
  • Prednisone 20 mg PO BID x 5 days then 10 mg PO BID x 5 days, then 10 mg PO QD x 5 days, then stop
• Maintenance treatment - intranasal steroids
• Surgical polypectomy - considered if steroids do not reduce polyps sufficiently (persistent obstruction or anosmia)
• Antibiotics
  • Doxycycline 200 mg PO on day 1 then 100 mg PO QD x 20 days - small reduction in polyp size
• Aspirin desensitization for AERD
• Omalizumab - in a small study of patients with comorbid asthma (+/- atopy), omalizumab x 4 months significantly decreased polyp size
• Cigarette smoke cessation
• Optimal treatment of allergic rhinitis (if present)

• Oral/topical antifungals suggested for persistent mucosal thickening and mucus production with no evidence of bacterial infection, who have failed intranasal steroids
  • Itraconazole (adults) 200 mg PO BID x 3 mos with AST/ALT qMo. If good response, continue with topical amphotericin B or itraconazole.

• Surgery - remove inspissated mucus and maximize sinus ventilation and drainage
• Post-surgery:
  • Prednisone 0.5 mg/Kg PO QD tapered over a few weeks to ~10 mg PO QD, then dose is slowly reduced by 1-2.5 mg/week to the lowest dose necessary to maintain control symptoms.
  • When mucosa has healed following surgery: Budesonide respules 0.5 mg/2mL vial + 5 mL saline (7 mL total) each nostril followed by head-positioning QD
  • Itraconazole 200 mg PO BID x 3-6 months (monitor LFTs QMo), then wean and maintain on topical steroid irrigation
  • Schubert: Prednisone 0.5 mg/Kg/d PO x 2 wks, then 0.5 mg/Kg PO QOD x 2 weeks, then taper to 5-7.5 mg/day PO over 3 months, and then continue on this dose for up to a year. Use short bursts of prednisone for any intercurrent exacerbation. If AFS requires repeat surgery restart prednisone protocol.
• Cigarette smoke cessation
• Optimal treatment of allergic rhinitis

• Topical amphotericin B or itraconazole should be considered optional unproved treatments for AFRS
• Allergen immunotherapy for fungus (based on positive SPT or sIgE) - may be safe and reduce disease recurrence

• Nasal saline lavage >200 mL each nostril QD to multiple times daily
• Intranasal topical steroids
  • Nasal spray (Flonase, Nasonex, Rhinocort) up to 2 sprays each nostril BID
  • If symptoms persist: Budesonide respules 0.5 mg/2mL vial + 5 mL saline (7 mL total) each nostril followed by head-positioning QD
  • LTRA - adjunct to intranasal steroids
• Intensive medical treatment - initial approach to patient with CRSsNP
  • Prednisone 20 mg PO BID x 5 days, then 20 mg PO QD x 5 days
  • Oral antibiotics x 3-4 weeks; extend up to 6 weeks if symptoms not entirely resolved at end of course (or continue antibiotics for 1 week after symptoms cleared)
    • Antibiotic choice guided by culture from middle meatus or other sinus ostium
    • Empiric antibiotics to cover common organisms:
      • Amox-clav 500 mg PO TID, 875 mg PO BID, OR 1000 mg ER PO BID
      • Clindamycin 450 mg PO TID
      • Moxifloxacin 400 mg PO QD
      • If MRSA suspected: Clindamycin, or metronidazole plus TMP-SMX or linezolid
      • If refractory: Metronidazole plus cefuroxime, cefdinir, cefpodoxime, levofloxacin (adults), azithromycin, clarithromycin, or TMP-SMX
  • Alternative to prednisone/antibiotics is long term macrolides x 3 months
  • In a study of children (6-17 years old), the following regimen for intensive medical treatment of CRSsNP was effective and well-tolerated:
    • Amox/clav at 45/6.4 mg/kg/d (maximum, 2000/285 mg/d) x 30 days
    • Methylprednisolone PO taper x first 15 days according to the following schedule: 1 mg/kg/d (maximum, 40 mg/d) for 10 days, 0.75 mg/kg/d for 2 days, 0.5 mg/kg/d for 2 days, and 0.25 mg/kg/d for 1 day
• Additional course of intensive medical treatment for incomplete improvement in symptoms/CT findings if no clear indication for surgery and no alternative diagnosis. If second course fails then sinus surgery is logical next step.
• Maintenance treatment: intranasal steroids + nasal saline lavage
• Cigarette smoke cessation
• Optimal treatment of allergic rhinitis (if present)

• Topical itraconazole or amphotericin-B: suggested for persistent mucosal thickening and mucus production with no evidence of bacterial infection, who have failed intranasal steroids